1. Field of the Invention
The present invention relates to tissue-supporting medical devices, and more particularly to expandable, non-removable devices that are implanted within a bodily lumen of a living animal or human to support the organ and maintain patency, and that have improved spatial distribution for delivery of a beneficial agent to the intervention site.
2. Summary of the Related Art
In the past, permanent or biodegradable devices have been developed for implantation within a body passageway to maintain patency of the passageway. These devices are typically introduced percutaneously, and transported transluminally until positioned at a desired location. These devices are then expanded either mechanically, such as by the expansion of a mandrel or balloon positioned inside the device, or expand themselves by releasing stored energy upon actuation within the body. Once expanded within the lumen, these devices, called stents, become encapsulated within the body tissue and remain a permanent implant.
Known stent designs include monofilament wire coil stents (U.S. Pat. No. 4,969,458); welded metal cages (U.S. Pat. Nos. 4,733,665 and 4,776,337); and, most prominently, thin-walled metal cylinders with axial slots formed around the circumference (U.S. Pat. Nos. 4,733,665; 4,739,762; and 4,776,337). Known construction materials for use in stents include polymers, organic fabrics and biocompatible metals, such as, stainless steel, gold, silver, tantalum, titanium, and shape memory alloys such as Nitinol.
U.S. Pat. Nos. 4,733,665; 4,739,762; and 4,776,337 disclose expandable and deformable interluminal vascular grafts in the form of thin-walled tubular members with axial slots allowing the members to be expanded radially outwardly into contact with a body passageway. After insertion, the tubular members are mechanically expanded beyond their elastic limit and thus permanently fixed within the body. U.S. Pat. No. 5,545,210 discloses a thin-walled tubular stent geometrically similar to those discussed above, but constructed of a nickel-titanium shape memory alloy (xe2x80x9cNitinolxe2x80x9d), which can be permanently fixed within the body without exceeding its elastic limit. All of these stents share a critical design property: in each design, the features that undergo permanent deformation during stent expansion are prismatic, i.e., the cross sections of these features remain constant or change very gradually along their entire active length. These prismatic structures are ideally suited to providing large amounts of elastic deformation before permanent deformation commences, which in turn leads to sub-optimal device performance in important properties including stent expansion force, stent recoil, strut element stability, stent securement on delivery catheters and radiopacity.
U.S. Pat. No. 6,241,762 which is incorporated herein by reference in its entirety, discloses a non-prismatic stent design which remedies the above mentioned performance deficiencies of previous stents. In addition, preferred embodiments of this patent provide a stent with large, non-deforming strut and link elements, which can contain holes without compromising the mechanical properties of the strut or link elements, or the device as a whole. Further, these holes may serve as large, protected reservoirs for delivering various beneficial agents to the device implantation site.
Of the many problems that may be addressed through stent-based local delivery of beneficial agents, one of the most important is restenosis. Restenosis is a major complication that can arise following vascular interventions such as angioplasty and the implantation of stents. Simply defined, restenosis is a wound healing process that reduces the vessel lumen diameter by extracellular matrix deposition and vascular smooth muscle cell proliferation and which may ultimately result in renarrowing or even reocclusion of the lumen. Despite the introduction of improved surgical techniques, devices and pharmaceutical agents, the overall restenosis rate is still reported in the range of 25% to 50% within six to twelve months after an angioplasty procedure. To treat this condition, additional revascularization procedures are frequently required, thereby increasing trauma and risk to the patient.
Several techniques under development to address the problem of restenosis are irradiation of the injury site and the use of conventional stents to deliver a variety of beneficial or pharmaceutical agents to the traumatized vessel lumen. In the latter case, a conventional stent is frequently surface-coated with a beneficial agent (often a drug-impregnated polymer) and implanted at the angioplasty site. Alternatively, an external drug-impregnated polymer sheath is mounted over the stent and co-deployed in the vessel.
While acute outcomes from radiation therapies appeared promising initially, long term beneficial outcomes have been limited to restenosis occurring within a previously implanted stent, so-called xe2x80x98in-stentxe2x80x99 restenosis. Radiation therapies have not been effective for preventing restenosis in de novo lesions. Polymer sheaths that span stent struts have also proven problematic in human clinical trials due to the danger of blocking flow to branch arteries, incomplete apposition of stent struts to arterial walls and other problems. Unacceptably high levels of MACE (Major Adverse Cardiac Events that include death, heart attack, or the need for a repeat angioplasty or coronary artery bypass surgery) have resulted in early termination of clinical trials for sheath covered stents.
Conventional stents with surface coatings of varius beneficial agents, by contrast, have shown promising early results. U.S. Pat. No. 5,716,981, for example, discloses a stent that is surface-coated with a composition comprising a polymer carrier and paclitaxel (a well-known compound that is commonly used in the treatment of cancerous tumors). The patent offers detailed descriptions of methods for coating stent surfaces, such as spraying and dipping, as well as the desired character of the coating itself: it should xe2x80x9ccoat the stent smoothly and evenlyxe2x80x9d and xe2x80x9cprovide a uniform, predictable, prolonged release of the anti-angiogenic factor.xe2x80x9d Surface coatings, however, can provide little actual control over the release kinetics of beneficial agents. These coatings are necessarily very thin, typically 5 to 8 microns deep. The surface area of the stent, by comparison is very large, so that the entire volume of the beneficial agent has a very short diffusion path to discharge into the surrounding tissue. The resulting cumulative drug release profile is characterized by a large initial burst, followed by a rapid approach to an asymptote, rather than the desired xe2x80x9cuniform, prolonged release,xe2x80x9d or linear release.
Increasing the thickness of the surface coating has the beneficial effects of improving drug release kinetics including the ability to control drug release and to allow increased drug loading. However, the increased coating thickness results in increased overall thickness of the stent wall. This is undesirable for a number of reasons, including increased trauma to the vessel lumen during implantation, reduced flow cross-section of the lumen after implantation and increased vulnerability of the coating to mechanical failure or damage during expansion and implantation. Coating thickness is one of several factors that affect the release kinetics of the beneficial agent, and limitations on thickness thereby limit the range of release rates, durations, and the like that can be achieved.
Recent research described in a paper titled xe2x80x9cPhysiological Transport Forces Govern Drug Distribution for Stent-Based Deliveryxe2x80x9d by Chao-Wei Hwang et al. has revealed an important interrelationship between the spatial and temporal drug distribution properties of drug eluting stents, and cellular drug transport mechanisms. In pursuit of enhanced mechanical performance and structural properties stent designs have evolved to more complex geometries with inherent inhomogeneity in the circumferential and longitudinal distribution of stent struts. Examples of this trend are the typical commercially available stents which expand to a roughly diamond or hexagonal shape when deployed in a bodily lumen. Both have been used to deliver a beneficial agent in the form of a surface coating. Studies have shown that lumen tissue portions immediately adjacent to the struts acquire much higher concentrations of drug than more remote tissue portions, such as those located in the middle of the xe2x80x9cdiamondxe2x80x9d shaped strut cells. Significantly, this concentration gradient of drug within the lumen wall remains higher over time for hydrophobic beneficial agents, such as paclitaxel or rapamycin, which have proven to be the most effective anti-proliferatives to date. Because local drug concentrations and gradients are inextricably linked to biological effect, the initial spatial distribution of the beneficial agent sources (the stent struts) is key to efficacy.
U.S. Pat. No. 5,843,120 discloses an expandable device comprising two groups of deformable elements. The first groups comprise a cylindrical arrays of generally parallel struts connected at alternating strut ends, or junctions, which accommodate radial (circumferential) expansion of the device. Even and odd first groups of struts are specified such that odd first groups are shifted circumferentially so as to be xe2x80x9c180xc2x0 degrees out of phasexe2x80x9d with even first groups, i.e., with strut junctions of even first groups directly opposed to strut junctions of odd first groups. The second groups of elements are generally flexible bridging elements that connect the junctions of even and odd first groups. This configuration gives rise to the common xe2x80x9cdiamondxe2x80x9d pattern of struts in stent expansion. One frequently used index of the distance of the most distant lumen tissue portions from the nearest drug-eluting element is the xe2x80x9cinscribed circle.xe2x80x9d This is simply the largest circle that can be inscribed in the open cell area bordered by a given set of strut elements, for example, the largest circle that could be inscribed in the diamond pattern cell described above. Smaller inscribed circles, indicating shorter drug diffusion paths and correspondingly lower concentration variations, are more desirable.
A central feature of U.S. Pat. No. 5,843,120 is that the bridging elements (second group elements) are configured to expand along the longitudinal axis of the device to compensate for the longitudinal contraction that occurs in the first groups of struts when the device is expanded radially, so that the device does not undergo overall longitudinal contraction during radial expansion. This property of the device leads to further inhomogeneity in the spatial distribution of the beneficial agent. The bridging elements generally have a substantially smaller width (for flexibility) than the first groups of struts, and have a correspondingly smaller surface area for conveying beneficial agents in the form of coatings. During device expansion the even and odd first groups of struts, with their relatively high surface area, contract longitudinally, further concentrating drug in smaller annular slices of tissue. Conversely, the low surface area bridging elements expand longitudinally during expansion, effectively reducing the amount of beneficial agent deliver at the larger annular slices of tissue adjacent the bridging elements. The net effect of the longitudinally contracting first group of struts and longitudinally expanding bridging elements is to increase tissue concentration variations of the beneficial agent.
It would be desirable to provide a stent structure with smaller inscribed circles and corresponding lower beneficial agent concentration variations. It would also be desirable to provide a stent structure with more even beneficial agent concentration distributions between stent struts and bridging elements.
In view of the drawbacks of the prior art, it would be advantageous to provide a stent capable of delivering a relatively large volume of a beneficial agent to a traumatized site in a vessel lumen while avoiding the numerous problems associated with surface coatings containing beneficial agents, without increasing the effective wall thickness of the stent, and without adversely impacting the mechanical expansion properties of the stent.
It would further be advantageous to have a tissue supporting device which improves the spatial distribution of beneficial agents in lumen tissue by decreasing the mean and maximum distances between lumen tissue portions and agent-eluting elements of the device, while staying within the desirable range of ratios of device area to lumen tissue area and allowing side branch perfusion.
In accordance with one aspect of the invention, an expandable medical device includes a plurality of elongated struts, the plurality of elongated struts joined together to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, wherein adjacent ones of the plurality of elongated struts are substantially parallel when the cylinder is at the first diameter and the adjacent elongated struts form V-shapes when the cylinder is at the second diameter, and a plurality of pivots joining the plurality of struts together in the substantially cylindrical device, wherein only one pivot interconnects each two adjacent elongated struts and the pivots are each located offset from a line bisecting the V-shapes formed by the elongated struts when the cylinder is at the second diameter.
In accordance with a further aspect of the present invention, an expandable medical device includes a plurality of elongated struts, the plurality of elongated struts joined together to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, wherein adjacent ones of the plurality of elongated struts are substantially parallel when the cylinder is at the first diameter and the adjacent elongated struts form V-shapes when the cylinder is at the second diameter, and a plurality of ductile hinges connecting the plurality of struts together in the substantially cylindrical device, wherein only one ductile hinge interconnects each two adjacent elongated struts and the ductile hinges are each located offset from a line bisecting the V-shapes formed by the elongated struts when the cylinder is at the second diameter, the ductile hinges having a hinge width which is smaller than a strut width such that as the device is expanded from the first diameter to the second diameter the ductile hinges experience plastic deformation while the struts are not plastically deformed.
In accordance with another aspect of the present invention, an expandable medical device includes a plurality of cylindrical members which are expandable from a cylinder having a first diameter to a cylinder having a second diameter, each of the plurality of cylindrical members comprising a plurality of L-shaped struts and a plurality of ductile hinges, wherein each of the plurality of L-shaped struts is joined to an adjacent L-shaped strut by a ductile hinge, and wherein a width of the ductile hinges is smaller than a width of the L-shaped struts such that as the plurality of cylindrical members are expanded from the first diameter to the second diameter the ductile hinges experience plastic deformation while the L-shaped struts are not plastically deformed and a plurality of bridging members connecting the L-shaped struts of adjacent cylindrical members to form an expandable device configured for radial expansion while a longitudinal distance between ends of the plurality of cylindrical members does not increase.
In accordance with an additional aspect of the present invention, an expandable medical device includes a plurality of struts each having a long leg, a short leg connected to the long leg, and a connecting point, wherein the long leg has a length longer than a length of the short leg, a plurality of pivots joining the long leg of one strut to the short leg of an adjacent strut to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, wherein as the substantially cylindrical device is expanded from the first diameter to the second diameter the pivots bend, and a plurality of bridging members connected to the connecting points of struts in one row and to the connecting points of struts in an adjacent row to form an expandable device configured such that a total length of the bridging members remains substantially constant during radial expansion.
In accordance with another aspect of the present invention, an expandable medical device includes a plurality of elongated struts, the plurality of elongated struts joined together by pivoting connections to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, wherein adjacent ones of the plurality of elongated struts are substantially parallel when the cylinder is at the first diameter and the adjacent elongated struts form a plurality of substantially parallelogram shapes when the cylinder is at the second diameter.
In accordance with a further aspect of the present invention, an expandable medical device for delivery of a beneficial agent includes a plurality of elongated struts, the plurality of elongated struts joined together by pivoting connections to form a substantially cylindrical device which is expandable from a cylinder having a first diameter to a cylinder having a second diameter, wherein adjacent ones of the plurality of elongated struts are substantially parallel when the cylinder is at the first diameter and the adjacent elongated struts form a plurality of substantially parallelogram shapes when the cylinder is at the second diameter, and a beneficial agent affixed to the plurality of struts for delivery to tissue.